In the field of PDT, various tetrapyrrolic purpurins, chlorins, phthalocyanines and benzochlorins have shown the ability both to localize at a tumor site and to absorb light to form an activated state in response to the light. Of particular interest are the compounds which absorb light in the red region of the spectrum (600 to 800 nm), which more easily penetrates bodily tissues. Thus, the various functionalities of these photosensitizers can be altered to increase the efficiency of tumor necrosis. One class of these red-absorbing compounds is the 5,15-(p-substituted)diaryl benzochlorins, and related formyl-substituted porphyrins, which display major absorptions in the 500-710 nm region.
It is known that nickel(II) or copper(II) porphyrins, such as copper(II) octaethylporphyrin, may be treated with 3-(dimethylamino)acrylaldehyde ("3-DMA") and phosphoryl chloride (POCl.sub.3) to form the corresponding meso-(2-formylvinyl)porphyrins. These reactions are commonly known as Vilsmeier Reactions. Further, when these compounds are subjected to strong acid treatment, the aldehyde portion cyclizes to form a fused benzene ring, giving the corresponding benzochlorins, as shown below: ##STR2## where M is Ni or Cu. Arnold et al., "Wittig Condensation Products from Nickel meso-Formyl-octaethylporphyrin and -aetioporphyrin I and Some Cyclisation Reactions," J.C.S. Perkin I, 1660-70 (1978); Vicente et al., "Efficient New Syntheses of Benzochlorins, Benzoisobacteriochlorins, and Benzobacteriochlorins," Tetrahedron Letters, 31, 1365-68 (1990); and Vicente et al., "Vilsmeier Reactions of Porphyrins and Chlorins with 3-(Dimethylamino)acrolein to Give meso-(2-Formylvinyl)porphyrins: New Syntheses of Benzochlorins, Benzoisobacteriochlorins, and Benzobacteriochlorins and Reductive Coupling of Porphyrins and Chlorins Using Low-Valent Titanium Complexes," J. Org. Chem. 56, 4407-18 (1991).
Recently, 5,15-diaryl porphyrins have been treated with the Vilsmeier reagent (3-DMA/POCl.sub.3) to form the corresponding meso-(2-formylvinyl)porphyrins, which have been cyclized to form the corresponding benzochlorins substituted with two aryl rings, one in the 5-position and the other in the 15-position. Osuka et al., "Synthesis of Benzochlorin Monomer, Dimer, and Porphyrin-Benzochlorin Heterodimer from 5-Aryl- and 5,15-Diaryloctaethylporphyrins," Bull. Chem. Soc. Jpn., 65, 3322-30 (1992). Some of these derivatives have shown strong absorptions in the visible region around 700 nm, due to the modification of the porphyrin chromophore. Further, the presence of the two aryl rings on the structures of these compounds allows for flexibility in design to adjust for such properties as hydrophobicity, water solubility, and electrochemical and photophysical properties. Gunter, "5,15-Diaryl Substituted Benzochlorins--Synthesis and Structure," Tetrahedron 47, 7853-68 (1991).
In all of the above-described methods, however, the presence of substituents at the pyrrolic .beta.-positions adjacent to the benzenoid ring formed in the cyclization reaction causes the formation of a product that is either dialkyl substituted or hydroxyalkyl substituted at the .beta.-position. When there are no substituents at either of the peripheral .beta.-positions where the benzenoid ring will be formed during cyclization, ring closure causes the formation of a reaction mixture containing more than one compound, probably including, among other things, a secondary alcohol intermediate as opposed to a tertiary alcohol. This intermediate reaction mixture is then susceptible to oxidation to form a ketone. Thus, it has now been discovered that, in this way, a carbonyl chromophoric unit can be added to the benzochlorin nucleus, causing an even further bathochromic shift and an improved intensification of the Q band of longest wavelength.